Abstract
The relationship between primary sequence and collagen triple‐helix formation is relatively well characterized, while higher levels of structural assembly from these sequences is poorly understood. To address this gap, a new collagen‐like triblock peptide design was used to study the relationship between amino acid sequence and supramolecular assembly. Four collagen‐like peptides with the sequence (Glu)~5~(Gly–Xaa–Hyp–Gly–Pro–Hyp)~6~(Glu)~5~ and corresponding to Xaa = alanine, proline, serine, or valine, and an analogous peptide without the glutamic acid end blocks, were solubilized in water at high concentrations (20–150 mg/mL) and analyzed in optical polarizing microscopy and transmission electron microscopy. Some of the peptides self‐assembled into supramolecular structures, the nature of which was determined by the core collagen‐like sequence. The globular end blocks appeared necessary for these short triple‐helix‐forming peptides to spontaneously organize into supramolecular structures in solution and also provided enhanced thermal stability based on CD analysis. The results indicate a strong dependence of the peptide triblock assembly behavior on the identity of the guest residue Xaa; nematic order when Xaa was valine, no organization when Xaa was serine, and banded spherulites displaying a cholesteric‐like twist when Xaa was proline or alanine. According to these results, the identity of the amino acid in position Xaa of the triplet Gly–Xaa–Yaa dramatically determined the type of supramolecular assembly formed by short triple helices based on collagen‐triblock like sequences. Moreover, the structural organization observed for these collagen‐triblock peptides was analogous to some assemblies observed for native collagen in vivo and in vitro. The amino acid sequence in the native collagen proteins may therefore be a direct determinant of the different supramolecular architectures found in connective tissues. © 2003 Wiley Periodicals, Inc. Biopolymers 70:435–444, 2003